Citric Acid → HCID 59279527, compound

HRID 1098199Notes

Reaction equation

HRID 1098199 reaction equation
[H-].[Na+].[Si:3]([O:20][CH2:21][CH2:22][O:23][CH2:24][C@H:25]([OH:30])[C:26]([O:28][CH3:29])=[O:27])([C:16]([CH3:19])([CH3:18])[CH3:17])([C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.Cl[C:32]1[N:37]=[CH:36][N:35]=[C:34]2[N:38]([C:41]3[CH:46]=[C:45]([CH3:47])[CH:44]=[CH:43][C:42]=3[CH3:48])[N:39]=[CH:40][C:33]=12.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>C1COCC1>[Si:3]([O:20][CH2:21][CH2:22][O:23][CH2:24][C@H:25]([O:30][C:32]1[N:37]=[CH:36][N:35]=[C:34]2[N:38]([C:41]3[CH:46]=[C:45]([CH3:47])[CH:44]=[CH:43][C:42]=3[CH3:48])[N:39]=[CH:40][C:33]=12)[C:26]([O:28][CH3:29])=[O:27])([C:16]([CH3:19])([CH3:18])[CH3:17])([C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)[C:4]1[CH:5]=[CH:6][CH:7]=[CH:8][CH:9]=1

Participants

6

Reactant 4

HCID 311Citric AcidHCID 24758Sodium hydrideHCID 431548064-chloro-1-(2,5-dimethylphenyl)-1H-pyrazolo[3,4-d]pyrimidineHCID 59279512(S)-methyl 3-(2-(tert-butyldiphenylsilyloxy)ethoxy)-2-hydroxypropanoate

Product 1

HCID 59279527HCID 59279527, compoundYield 57.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

60% sodium hydride (0.187 g, 4.67 mmol) was added to (S)-methyl 3-(2-(tert-butyldiphenylsilyloxy)ethoxy)-2-hydroxypropanoate (Intermediate AB3) (1.568 g, 3.90 mmol) in anhydrous THF (20 mL) at 0° C. under nitrogen. The resulting solution was stirred at 0° C. for 10 minutes and then 4-chloro-1-(2,5-dimethylphenyl)-1H-pyrazolo[3,4-d]pyrimidine (Intermediate AJ3)(1.008 g, 3.90 mmol) was added. The reaction mixture was allowed to warm to room temperature and stirred for 1 hour. The reaction mixture was neutralised with 1M citric acid and the majority of the THF removed in vacuo. The residue was diluted with water (20 mL) and EtOAc (100 mL). The organic layer was separated and the aqueous layer re-extracted with EtOAc (100 mL). The combined organics were washed with saturated brine (75 mL), dried (MgSO4) and evaporated to give the crude product. This was purified by flash silica chromatography, elution gradient 0 to 20% EtOAc in isohexane to afford the product (1.400 g, 57.5%). m/z (ES+) (M+H)+=625; HPLC tR=3.53 min.

Workup

  1. temperatureto warm to room temperature
  2. stirringstirred for 1 hour
  3. customthe majority of the THF removed in vacuo
  4. additionThe residue was diluted with water (20 mL) and EtOAc (100 mL)
  5. customThe organic layer was separated
  6. extractionthe aqueous layer re-extracted with EtOAc (100 mL)
  7. washThe combined organics were washed with saturated brine (75 mL)
  8. dry with materialdried (MgSO4)
  9. customevaporated
  10. customto give the crude product
  11. customThis was purified by flash silica chromatography, elution gradient 0 to 20% EtOAc in isohexane

Sources & evidence

ORD record
ord-2615db11abff4a3b9b8cfd89c079c42a
Source dataset
uspto-grants-2012_03
Patent number
US08143263B2

Reaction notes

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